The chemical name of Celecoxib is 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide and is a diaryl-substituted pyrazole. The molecular formula is C17H14F3N3O2S, and the molecular weight is 381.38; the chemical structure is as follows:

Celecoxib is a white powder, insoluble in water, soluble in methanol and chloroform.
CELEBREX oral capsules contain either 50 mg, 100 mg, 200 mg or 400 mg of Celecoxib, together with inactive ingredients including: croscarmellose sodium, edible inks, gelatin, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate.
CELEBREX is a nonsteroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of CELEBREX is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2), and at therapeutic concentrations in humans, CELEBREX does not inhibit the cyclooxygenase-1 (COX-1) isoenzyme. In animal colon tumor models, CELEBREX reduced the incidence and multiplicity of tumors.
Peak plasma levels of Celecoxib occur approximately 3 hrs after an oral dose. Under fasting conditions, both peak plasma levels (Cmax) and area under the curve (AUC) are roughly dose-proportional up to 200 mg BID; at higher doses there are less than proportional increases in Cmax and AUC. Absolute bioavailability studies have not been conducted. With multiple dosing, steady-state conditions are reached on or before Day 5.
When CELEBREX capsules were taken with a high fat meal, peak plasma levels were delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. Under fasting conditions, at doses above 200 mg, there is less than a proportional increase in Cmax and AUC, which is thought to be due to the low solubility of the drug in aqueous media.
Co-administration of CELEBREX with an aluminum- and magnesium-containing antacids resulted in a reduction in plasma celecoxib concentrations with a decrease of 37% in Cmax and 10% in AUC. CELEBREX, at doses up to 200 mg twice daily, can be administered without regard to timing of meals. Higher doses (400 mg twice daily) should be administered with food to improve absorption.
In healthy adult volunteers, the overall systemic exposure (AUC) of Celecoxib was equivalent when Celecoxib was administered as intact capsule or capsule contents sprinkled on applesauce. There were no significant alterations in Cmax, tmax, or t1/2 after administration of capsule contents on applesauce.
In healthy subjects, Celecoxib is highly protein bound (˜97%) within the clinical dose range. In-vitro, studies indicate that Celecoxib binds primarily to albumin and, to a lesser extent, α1-acid glycoprotein. The apparent volume of distribution at steady state (Vss/F) is approximately 400 L, suggesting extensive distribution into the tissues. Celecoxib is not preferentially bound to red blood cells.
Celecoxib metabolism is primarily mediated via CYP2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors.
Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug recovered in the urine and feces. Following a single oral dose of radiolabeled drug, approximately 57% of the dose was excreted in the feces and 27% was excreted into the urine. The primary metabolite in both urine and feces was the carboxylic acid metabolite (73% of dose) with low amounts of the glucuronide also appearing in the urine. It appears that the low solubility of the drug prolongs the absorption process making terminal half-life (t½) determinations more variable. The effective half-life is approximately 11 hours under fasted conditions. The apparent plasma clearance (CL/F) is about 500 mL/min.
The main medical concerns surrounding Celecoxib are related to slow absorption and variable first-pass metabolism of Celecoxib limit its utility for treatment of acute pain. When a single dose of 200 mg of current formulation is given, peak plasma levels occur 3 hours after an oral dose, however, onset of pain relief could be as early as 1 hour. When taken with a high fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. Since it is a painkiller shortening this time and the elimination of the delay of peak plasma concentrations could be advantageous.
In order to overcome the problems associated with prior conventional Celecoxib formulations and available drug delivery systems, novel pharmaceutical compositions of Celecoxib comprising the pharmaceutical formulation of complexed Celecoxib and crystalline Celecoxib were prepared. The pharmaceutical formulation ensures the immediate absorption of Celecoxib via the complexed formulation, resulting in fast pain relief, while the crystalline component is responsible for delayed absorption and extended analgesic effect.
A variety of strategies have been used to attempt to overcome these issues, see for example US 20130338131, WO 2009114695, U.S. Pat. No. 7,879,360, US 20090098200, WO 2003080027, US 20150011514, U.S. Pat. No. 6,964,978, U.S. Pat. No. 7,220,867, WO 2001042221, WO 2001095877, WO 2001091750, WO 2014018932, WO 2004078163, WO 2004047752, WO 2007010559, WO 2013132457 and WO 2001041760.